Cancer causes about fifteen % of all human deaths worldwide. Early detection and treatment will lead to the improved survival for various cancers. However, the development of many cancers is still poorly understood, and drugs have not been proven to be generally efficient in the treatment of cancers. Positron emission tomography (PET) has been widely used in clinical oncology for tumor diagnosis, staging, and treatment monitoring. Development and clinical translation of novel, molecularly targeted PET tracers will facilitate future developments in personalized medicine for cancer patients, such as patient stratification and monitoring the therapeutic responses to anti-cancer drugs. Non-invasive PET imaging of tumor angiogenesis (e.g., new blood vessel formation) has gained tremendous interest over the last decade, since the development and metastasis of solid tumors depends on tumor angiogenesis.
Angiogenesis is a fundamental biological process involved in the growth of most solid tumors; as such, anti-angiogenic approaches, such as the development of angiogenesis inhibitors represents a promising strategy for cancer treatment, diagnosis, and prevention. Integrins, a family of heterodimeric cell surface receptors involved in a wide range of cell-cell and cell-extracellular matrix interactions, including tumor angiogenesis, have been active targets for development of anti-angiogenic therapies.
Among the many proteins involved in tumor angiogenesis and metastasis of solid tumors, integrin αvβ3 is one of the most intensively studied. Several PET tracers targeting this cell adhesion molecule have entered clinical investigation. Frequently overexpressed on the tumor neovasculature, as well as cancer cells of many tumor types (e.g., lung/prostate/breast cancer and glioblastoma), integrin αvβ3 is an attractive target for both cancer diagnosis and therapy. Integrin αvβ3 binds tightly to ECM proteins such as fibronectin, fibrinogen, and vitronectin, which contain the tripeptide sequence RGD (Arg-Gly-Asp), a prominent recognition motif involved in cell adhesion. Since αvβ3 is highly upregulated on the endothelium during tumor angiogenesis, peptides or small non-peptidic molecules mimicking the RGD recognition motif may represent promising anti-angiogenesis agents by targeting αvβ3 for cancer prevention or targeted diagnosis.